MedicalResearch.com Interview with:
Yingxi (Cimo) Chen, MD, MPH, PhDPostdoctoral FellowRadiation Epidemiology Branch, DCEG, NCI, NIHRockville MD 20850MedicalResearch.com: What is the background for this study? Response: Death rates from drug overdose have more than doubled in the US in the 21st century. Similar increases in drug overdose deaths have been reported in other high-income countries but few studies have compared rates across countries.(more…)
MedicalResearch.com Interview with:
Joceline Vu, MD
Resident, PGY-5
Department of Surgery
University of MichiganMedicalResearch.com: What is the background for this study? What are the main findings?Response: This study examined how much opioid patients use after surgery, and looked at factors that might predispose some patients to use more or less.
Patient opioid use after surgery is an interesting question that’s gained a lot of attention recently, because it’s different from other uses for opioids. If you have chronic pain, you’re probably going to use all of your prescription. But if you have surgery, you may not take all of your pills, and this leaves people with leftover pills that can be dangerous later.
From this study, we found that patients only use, on average, about quarter of their prescription, meaning that a lot of them are left with leftover pills. Moreover, we found that the biggest determinant of how much they used wasn’t how much pain they reported, or any other factor—it was how big their original prescription was.
What this means is that opioid use after surgery isn’t just determined by pain, but also by what surgeons prescribe. It’s important to keep this in mind as we try to reduce unnecessary opioid prescribing after surgical procedures.(more…)
MedicalResearch.com Interview with:
Troy Quast, PhD
Associate Professor in the University
South Florida College of Public Healt
MedicalResearch.com: What is the background for this study? What are the main findings?Response: One of the cited repercussions of the opioid epidemic is its effect on families. However, there is considerable variation in opioid misuse across the county. This is the first nation-wide study to investigate the relationship between opioid prescription rates and child removals at the state level.
I found that there are significant differences across states in the relationship between opioid prescription and child removal rates associated with parental substance abuse. In twenty-three states, increases in opioid prescription rates were associated with increases in the child removal rate. For instance, in California a 10% increase in the county average prescription rate was associated with a 28% increase in the child removal rate. By contrast, in fifteen states the association was flipped, where increases in the opioid prescription rate were associated with decreases in the child removal rate. There was no statistically significant relationship in the remaining states.(more…)
MedicalResearch.com Interview with:
Joshua Barocas, MD
Assistant Professor of Medicine
Section of Infectious Diseases
Boston Medical Center / Boston University School of MedicineMedicalResearch.com: What is the background for this study? What are the main findings?Response: Massachusetts has been particularly hard hit by the opioid epidemic despite lower opioid prescribing rates, near universal health insurance, and availability of opioid treatment. That said, it is difficult to estimate the population with or at-risk for opioid use disorder. It is generally a highly stigmatized disease and typical methods to estimate of opioid use disorder relay on contact with the healthcare system and/or patient reporting.
We used a unique and powerful methodology coupled with a first-in-the-nation linked database in Massachusetts to obtain both an accurate count of people with opioid use disorder who are known to the healthcare system and estimate the number who are out there but not yet known to the system.
We found that more than 275,000 people – or 4.6 percent of people over the age of 11 in Massachusetts– have opioid use disorder, a figure nearly four times higher than previous estimates based on national data. In 2011 and 2012, the prevalence of opioid use disorder in Massachusetts for those over the age of 11 was 2.72 percent and 2.87 percent, respectively. That increased to 3.87 percent in 2013, and even more, to 4.6 percent in 2015. Those between the ages of 11 and 25 experienced the greatest increase in prevalence of all age groups. The number of “known” persons increased throughout the study period – from 63,989 in 2011 to 75,431 in 2012, and 93,878 in 2013 to 119,160 in 2015.(more…)
MedicalResearch.com Interview with:
Jon Zibbell, PhD,
Senior public health scientistBehavioral Health Research Division
RTI International
Research Triangle Park, NC,MedicalResearch.com: What is the background for this study? What are the main findings?Response: For the first time in 2016, U.S. overdose deaths involving illicitly-manufactured fentanyl surpassed deaths from heroin and prescription deaths.
Fentanyl is an extremely potent synthetic opioid, and an illicitly-manufactured form of the drug is regularly being mixed with heroin and often sold to unwitting consumers. Fentanyl is 50 times more potent than heroin and its illicitly-manufactured version is extremely difficult to discern when mixed with heroin. Harm reduction organizations have started to distribute FTS and people consuming street-purchased opioids are using them to test drugs for fentanyl. Our objective was to assess whether this point-of-use form of drug checking was influencing people’s drug use behavior. The study was self-funded by the research institute RTI International.
Our findings show that consumers who tested street opioids with fentanyl test strips were five times more likely to engage in safer drug use behavior when the test comes back positive. The study was conducted among a group of 125 people who inject drugs in Greensboro, North Carolina.
(more…)
MedicalResearch.com Interview with:
Hanna Grol-Prokopczyk PhD
Assistant Professor, Department of Sociology
University at Buffalo, SUNY
MedicalResearch.com: What is the background for this study? Response: Studies examining predictors of prescription opioid use often have limited information about users’ socioeconomic status, their level of pain, and their opinions of opioids. Using unique data from the Health and Retirement Study’s 2005-2006 Prescription Drug Study—which includes information about older adults’ education, income, wealth, insurance type, pain level, and opinions of prescription drugs used—I was able to explore how socioeconomic factors shaped prescription opioid use in the 2000s, when U.S. opioid use was at its peak. I was also able to present a snapshot of how users of prescription opioids felt about these drugs before the declaration of an opioid epidemic.
(more…)
MedicalResearch.com Interview with:
David A. Shaye, M.D., FACS
Instructor in Otolaryngology
Harvard Medical SchoolMedicalResearch.com: What is the background for this study? What are the main findings?Response: Cosmetic and functional rhinoplasty (nasal surgery) is the most common procedure we perform and traditionally post operative pain medication includes opioids.
In light of the recent opioid epidemic, we wished to investigate if patients pain was being treated over-treated by surgeons.
Of 173 Rhinoplasties that we performed, the majority of patients received post operative opioid tablets (an average of 28 tablets). However 11% of patients did not fill these prescriptions at all, and only 2 of the 178 patients required refills.
We believe patients experienced less pain than surgeons anticipated.
(more…)
MedicalResearch.com Interview with:
Gery P. Guy Jr., PhD, MPH
Senior Health Economist
Division of Unintentional Injury
CDCMedicalResearch.com: What is the background for this study? Response: In response to the increasing harms and adverse outcomes from prescription opioids, the CDC released the Guideline for Prescribing Opioids for Chronic Pain in March 2016. The CDC Guideline recommends evidence-based practices for opioid use for patients age 18 years and older in primary care settings in treating chronic pain outside of active cancer treatment, palliative care, and end-of-life care.
This report analyzed the temporal changes in opioid prescribing following the release of the CDC Guideline.
(more…)
MedicalResearch.com Interview with:
Bikram Subedi, PhD
Assistant Professor of Analytical Chemistry
Murray State University, Murray KY
MedicalResearch.com: What is the background for this study? What are the main findings?Response: The USA is one of the major consumers of diverse neuropsychiatric and illegal drugs, and recently declared a national public health emergency on opioid abuse. Law enforcement typically utilized conventional methods of determining drug consumption rate which are based on survey questionnaire, hospital admissions, drug-related crime statistics, and self-reported information. Conventional methods typically underestimate the actual consumption rate of drugs.
Our new approach of determining consumption rates of drugs in community is time and cost effecting and comprehensive. Based on levels of drugs quantified from raw sewage, the per capita consumption rates of several illicit drugs including methamphetamine, amphetamine, cocaine, and THC in two communities of Western Kentucky (similar population and only ~50 miles apart) were significantly different. During special events such as July 4th and 2017 solar eclipse, the consumption rates were found even higher. The consumption rate of methamphetamine was among one of the highest ever reported in the country.(more…)
MedicalResearch.com Interview with:
Tara Gomes, MHSc
Li Ka Shing Knowledge Institute, St Michael’s Hospital,
The Institute for Clinical Evaluative Sciences
Leslie Dan Faculty of Pharmacy
Department of Health Policy, Management, and Evaluation
University of Toronto, Toronto, Ontario, CanadaMedicalResearch.com: What is the background for this study? Response: Pregabalin is a medication increasingly being prescribed to manage pain, however there is emerging evidence that this drug may increase one's risk of opioid overdose when prescribed with opioids.
(more…)
MedicalResearch.com Interview with:
Derek S. Mason, MPH
Colorado University School of Medicine
MD Candidate, Class of 2022
Anschutz Medical Campus, Aurora, CO
MedicalResearch.com: What is the background for this study? What are the main findings?Response: The background for this report stems from a focus group of veterinarians that was held and identified that opioid diversion could be occurring within clinics.
After this, we became concerned that human patients were indeed diverting opioids for abuse and misuse and we wanted to get a broader sense from the veterinary medical community if they had been aware of opioid diversion happening within their clinics.
Additionally, we noticed that there was a gap in the scientific literature on how the veterinary medical community feels about the opioid epidemic. As prescribers of opioids, we felt that their input was highly valuable and should be included in the discussion on how to prevent opioid abuse and misuse.(more…)
MedicalResearch.com Interview with:
Calista Harbaugh, MD
House Officer, General Surgery
Clinician Scholar, National Clinician Scholars Program
Research Fellow, Michigan Opioid Prescribing Engagement Network
University of MichiganMedicalResearch.com: What is the background for this study? What are the main findings?Response: Wisdom tooth extractions is one of the most common procedures among teens and young adults, with more than 3.5 million young people having wisdom teeth pulled every year.
This procedure is commonly paired with a prescription for opioid pain medication. As the opioid epidemic sweeps the nation, we must pay attention to the long term effects of opioid prescribing for even routine procedures. This is particularly important for wisdom tooth extraction where there is evidence that opioid pain medications may be no more effective than anti-inflammatories alone.
Using commercial insurance claims, we evaluated the association between receiving an opioid prescription with wisdom tooth extraction and developing new persistent opioid use in the year after the procedure. We found nearly a 3-fold increase in odds of persistent opioid use, attributable to whether or not an opioid was prescribed. This translates to nearly 50,000 young people developing new persistent opioid use each year from routine opioid prescribing for wisdom tooth extraction.
(more…)
MedicalResearch.com Interview with:
Mark Pirner, MD, PhD
Senior Medical Director
Clinical Research and Medical Affairs
US WorldMeds
MedicalResearch.com: What is the background for this announcement? How does lofexidine differ from other opioid withdrawal medications?
Response: LUCEMYRA™ (lofexidine) was FDA-approved on May 16 as the first and only non-opioid, non-addictive medication for the management of opioid withdrawal in adults.
LUCEMYRA mitigates the acute and painful symptoms of opioid withdrawal by suppressing the neurochemical surge in the brain that occurs when opioids are abruptly discontinued.
In clinical studies, patients receiving treatment with LUCEMYRA experienced greater symptom relief and were significantly more likely to complete their withdrawal. LUCEMYRA is not an opioid drug and is not a treatment for opioid use disorder; it should be used as part of a longer-term treatment plan.
(more…)
MedicalResearch.com Interview with:
Evan Schwarz, MD FACEP, FACMT
Associate Professor of Emergency Medicine
Medical Toxicology Fellowship Director
Section Chief Medical Toxicology
Advisory Dean in the Office of Student Affairs
Division of Emergency Medicine
Washington University School of MedicineMedicalResearch.com: What is the background for this study? What are the main findings?Response: Ketamine is being increasingly used in the emergency department (ED) for a variety of conditions, including as an analgesic. While its usage continues to increase, there are limited studies evaluating ketamine as an analgesic in the emergency department.
Most of the studies evaluating ketamine utilized it as an adjunct to an opioid, however, multiple recommendations on blogs and other websites recommend ketamine as a single agent. The purpose of the meta-analysis was to compare the analgesic effect of ketamine compared to an opioid in adult patients presenting with acute pain to the ED.
In this study, we found that ketamine was non-inferior to opioids. We also found that the number of severe adverse events to be similar between both groups.
(more…)
MedicalResearch.com Interview with:
Tyler WinkelmanMD, MSc Clinician-Investigator
Division of General Internal Medicine, Hennepin Healthcare
Center for Patient and Provider Experience, Hennepin Healthcare Research Institute
Assistant Professor
Departments of Medicine & Pediatrics
University of Minnesota
MedicalResearch.com: What is the background for this study? Response: Opioid overdose deaths continue to escalate, and there have been reports that jails and prisons are bearing the brunt of the opioid epidemic. However, it wasn’t known, nationally, how many people who use opioids were involved in the criminal justice system. We also didn’t have recent estimates of common physical and mental health conditions among people with different levels of opioid use.
We used two years of national survey data to understand these associations, which are critical in developing a public health response to the opioid epidemic.
(more…)
MedicalResearch.com Interview with:
[caption id="attachment_42890" align="alignleft" width="199"] Dr. Ugiliweneza[/caption]
Beatrice Ugiliweneza, PhD, MSPH
Assistant Professor
Kentucky Spinal Cord Injury Research Center
Department of Neurosurgery, School...
MedicalResearch.com Interview with:
Jeanine M. Buchanich, Ph.D.
Research associate
Professor in the University of Pittsburgh Graduate
School of Public Health’s Department of Biostatistics
MedicalResearch.com: What is the background for this study? What are the main findings?Response: In the U.S., cause of death codes are assigned by the National Center for Health Statistics (NCHS) using information reported by the coroner or medical examiner completing the death certificate. Drug-specific overdose deaths are identified by the contributory causes of death, which are categorized as “T codes” and are assigned based on the specific drugs recorded by the coroner or medical examiner completing the death certificate. A code of T50.9 means “other and unspecified drugs, medicaments and biological substances.”
My colleagues and I extracted death data by state for 1999 through 2015 from the NCHS’s Mortality Multiple Cause Micro-data Files. We grouped overdose deaths into opioid-related, non-opioid-related and unspecified codes. In five states – Alabama, Indiana, Louisiana, Mississippi and Pennsylvania – more than 35 percent of the overdose deaths were coded as unspecified.
We then calculated the change in percentage of overdose deaths that fell into each category from 1999 to 2015 by state. In those 17 years, opioid-related overdose deaths rose 401 percent, non-opioid-related overdose deaths rose 150 percent and unspecified overdose deaths rose 220 percent.
This allowed us to extrapolate how many of the unspecified overdose deaths were likely opioid-related. By our calculations, potentially 70,000 opioid-related overdose deaths were not included in national opioid-related mortality estimates since 1999 because coroners and medical examiners did not specify the drug that contributed to the cause of death when completing the death certificates.(more…)
MedicalResearch.com Interview with:
Gary A. Smith, MD, DrPH
Director, Center for Injury Research and Policy
Nationwide Children’s Hospital
Columbus, OH
MedicalResearch.com: What is the background for this study? Response: Buprenorphine is a prescription opioid medication commonly used to treat opioid use disorder. From 2005 to 2010, the annual number of individual patients who received a buprenorphine prescription increased from 100,000 to more than 800,000.Although buprenorphine is important for the treatment of opioid use disorder, pediatric exposure to this medication can result in serious adverse outcomes.
(more…)
MedicalResearch.com Interview with:
Bradley D. Stein MD PhD
Senior Physician Policy Researcher
Pittsburgh Office
Rand Corporation
MedicalResearch.com: What is the background for this study? Response: Increasing use of medication treatment for individuals with opioid use disorders, with medications like methadone and buprenorphine, is a critical piece of the nation’s response to the opioid crisis. Buprenorphine was approved by the FDA in 2002 for treatment of opioid use disorders, but there was little information about to what extent buprenrophine’s approval increased the number of Medicaid-enrollees who received medication treatment in the years following FDA approval nor to what extent receipt of such treatment was equitable across communities.
(more…)
MedicalResearch.com Interview with:
Inmaculada Hernandez, PharmD, PhD
Assistant Professor of Pharmacy and Therapeutics
University of Pittsburgh School of Pharmacy
Pittsburgh, PA 15261
MedicalResearch.com: What is the background for this study? Response: Prior research has found that taking opioids and benzodiazepines simultaneously increases the risk of overdose by 2 to 3 fold, when compared to opioid-use only.
However, prior to our study, it was unclear how the risk of overdose changes over time with the concurrent use of opioids and benzodiazepines.
(more…)
MedicalResearch.com Interview with:
Marc R. Larochelle, MD, MPH
Assistant Professor of Medicine
Boston University School of Medicine
Boston MDMedicalResearch.com: What is the background for this study? What are the main findings?Response: In this study we examined more than 17,000 individuals who survived an opioid overdose in Massachusetts between 2012 and 2014.
We were interested in identifying how many went on to receive one of the three FDA-approved medications for opioid use disorder (MOUD), and whether or not they were associated with mortality.
We found that only 3 in 10 received MOUD and that receipt of buprenorphine and methadone were associated with 40-60% reduction in all-cause and opioid-related mortality.
We found no association between naltrexone and mortality though the confidence of this conclusion is limited by the small number who received naltrexone in this cohort.
(more…)
MedicalResearch.com Interview with:
Herbie Duber, MD, MPH, FACEP
Associate Professor, Emergency Medicine
Adjunct Associate Professor Department of Global Health
Adjunct Associate Professor
Institute for Health Metrics and Evaluation
University of Washington
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Opioid use disorder (OUD) and opioid overdose deaths are a rapidly increasing public health crisis. In this paper, we review and synthesize current evidence on the identification, management and transition of patients from the emergency department (ED) to the outpatient setting and present several key recommendations.
For patients identified to haveOpioid use disorder, we recommend ED-initiated mediation-assisted therapy (MAT) with buprenorphine, an opioid agonist. Current evidence suggests that it safe and effective, leading to improved patient outcomes. At the same time, a coordinated care plan should be put into motion which combines MAT with a rapid transition to outpatient care, preferably within 72 hours of ED evaluation. Where possible, a warm handoff is preferred, as it has been shown in other settings to improve follow-up. Outpatient care should combine MAT, psychological interventions and social support/case management in order to maximize impact (more…)
MedicalResearch.com Interview with:
Dr. Katie Witkiewitz PhD
Professor, Department of Psychology
University of New Mexico
MedicalResearch.com: What are the main findings?Response: The main findings from our study indicate that individuals with alcohol dependence who misused opioids (e.g., used without a prescription or not as prescribed) had a significantly higher likelihood of relapse to heavy drinking during alcohol treatment and were drinking more alcohol during and following alcohol treatment. (more…)
MedicalResearch.com Interview with:
Dr. Stuart Lustig, M.D., M.P.H
National Medical Executive for Behavioral Health
Cigna
Dr. Lustig discusses Cigna’s efforts to curb the opioid epidemic.MedicalResearch.com: What is the background for the Applying American Society of Addiction Medicine Performance Measures in Commercial Health Insurance and Services Data study?Response: In 2016 Cigna announced a collaboration with the American Society of Addiction Medicine (ASAM) to improve treatment for people suffering from substance use disorders and establish performance measures and best practices for addiction treatment. Mining anonymized data from Cigna’s administrative data, Brandeis University researchers have validated a new way to hone in on trouble spots where substance use disorder treatment for opioid, alcohol and other drug dependence is suboptimal, like the way police departments use computers to identify high crime areas in need of greater scrutiny and attention.
The technique uses ASAM-defined performance measures to assess substance use disorder treatment patterns, giving researchers the ability to sort through administrative data and measure to the extent to which patients being treated for opioid or alcohol use disorder are receiving and using evidenced-based medications proven to be effective in improving outcomes and retention in treatment. It also measures whether those patients received support during substance withdrawal – a critical factor in the success of addiction treatment plans. The performance measures were first tested on the Veterans’ Health Administration in 2016 and now, on data from Cigna.
(more…)
MedicalResearch.com Interview with:
Jason Kennedy, MS
Research project manager
Department of Critical Care Medicine
University of Pittsburgh
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Most previous studies of opioid use in health care have focused on the outpatient setting. But opioids are often introduced during hospitalization. That’s something clinicians can control, so we looked at inpatient prescription of these drugs to identify targets that may reduce opioid use once patients are out of the hospital.
We analyzed the medical records of 357,413 non-obstetrical adults hospitalized between 2010 and 2014 at 12 University of Pittsburgh Medical Center (UPMC) hospitals in southwestern Pennsylvania. The region is one of the areas of the country where opioid addiction is a major public health problem. We focused on the 192,240 patients who had not received an opioid in the year prior to their hospitalization – otherwise known as “opioid naïve” patients.
Nearly half (48 percent) of these patients received an opioid while hospitalized. After discharge, those patients receiving hospital opioids were more than twice as likely to report outpatient opioid use within 90-days (8.4 percent vs. 4.1 percent). Patients who receive an opioid for most of their hospital stay and patients who are still taking an opioid within 12 hours of being discharged from the hospital appear more likely to fill a prescription for opioids within 90 days of leaving the hospital.(more…)
MedicalResearch.com Interview with:
Scott E. Hadland, MD, MPH, MS
Assistant Professor of Pediatrics | Boston University School of Medicine
Boston Medical Center
Director of Urban Health & Advocacy Track | Boston Combined Residency Program
Boston, MA 02118
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Numerous pharmaceutical companies have received media attention for their role in promoting opioid prescribing through speaker programs and other marketing plans in which large-value payments are given to a small number of doctors to promote opioids.
In our study, we sought to tell the other side of the story. We wanted to identify whether low-value marketing, including industry-sponsored meals, which are commonplace in the US, were associated with increased opioid prescribing.
We found that 1 in 14 doctors received opioid marketing from pharmaceutical companies in 2014, and those that received marketing prescribed 9% more opioids the following year. With each additional meal a doctor received, he or she prescribed more and more opioids the following year. Our sample included 43% of the active physician workforce in the US, suggesting how widespread and far-reaching this effect might be.
(more…)
MedicalResearch.com Interview with:
Matthew A. Davis, MPH, PhD
Assistant Professor
Department of Systems, Populations and Leadership
University of Michigan
MedicalResearch.com: What is the background for this study? What are the main findings?Response: The premise for the study was based on prior work that demonstrated that the likelihood of being prescribed an opioid differs according to a patient’s race and ethnicity. Collectively this work has shown that Non-Hispanic Whites are more likely to receive opioids than other groups for pain.
We decided to look at trends in the prescribing of different pain medications over the last 16 years to see if we could detect any differences in prescribing patterns among racial and ethnic groups. To do so we used national health data for a large sample of Americans who live with significant pain.
(more…)
MedicalResearch.com Interview with:
Paul A. Moore, DMD, PhD, MPH
School of Dental Medicine
University of PittsburghMedicalResearch.com: What is the background for this study? What are the main findings?Response: Effective pain management is a priority in dental practice. Government and private agencies highlight the need to provide optimal pain relief, balancing potential benefits and harms of both opioid and nonopioid analgesic agents. The purpose of our study is to summarize the available evidence on the benefits and harms of analgesic agents, focusing on preexisting systematic reviews.
We found combinations of ibuprofen and acetaminophen as having the highest association with treatment benefit in adult patients and the highest proportion of adult patients who experienced maximum pain relief. Diflunisal, acetaminophen, and oxycodone were found to have the longest duration of action in adult patients. Medication and medication combinations that included opioids were among those associated most frequently with acute adverse events in both child and adult-aged patient populations.
(more…)
MedicalResearch.com Interview with:
Maria Sullivan, M.D., Ph.D
Senior Medical Director of Clinical Research and Development
Alkermes
MedicalResearch.com: What is the background for this study? Response: Extended release injectable naltrexone is approved for the prevention of relapse to opioid dependence after detoxification and when used with counseling. It is recommended that patients abstain from opioids for a minimum of seven to 10 days prior to induction onto XR-naltrexone to avoid precipitating opioid withdrawal. This requirement of detoxification represents a substantial clinical challenge, particularly in the outpatient setting.
There is currently no single recognized best method for opioid detoxification prior to first dose of extended-release naltrexone (XR-naltrexone). A number of induction regimens have been explored, including the use of low doses of oral naltrexone to shorten the transition period from dependence on opioids to XR-naltrexone treatment. The goal of the study was to help establish an outpatient regimen to transition subjects from physiological opioid dependence to XR-naltrexone treatment and mitigate the severity of opioid withdrawal symptoms.
We hypothesized that low-dose oral naltrexone, combined with buprenorphine and psychoeducational counseling, would assist with the transition of patients with opioid use disorder onto XR-naltrexone. In this 3-arm trial, we examined the utility of oral naltrexone, buprenorphine, and a fixed regimen of ancillary medications (oral naltrexone + buprenorphine vs. oral naltrexone + placebo buprenorphine vs. placebo +placebo), to determine whether any of these regimens was associated with higher rates of induction onto XR-naltrexone.
(more…)
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